Changes in serum inflammatory factors occur throughout the onset and multiple myeloma (MM) progression, the feedback loops make it harder to distinguish between causes and effects. In the present ...study, we performed a bidirectional summary‐level Mendelian randomization (MR) analysis to elucidate the causal relationships of C‐reactive protein (CRP) and inflammatory regulators with MM. Summary‐level data of genetic variants associated with inflammation were extracted from two genome‐wide association studies (GWASs) on CRP and human cytokines, while data on MM was from large meta‐analyses of GWASs among 372 617 UK Biobank participants. The inverse‐variance weighted (IVW) method was used as the primary MR analysis and MR‐Egger, weighted median, and MR‐pleiotropy residual sum and outlier (MR‐PRESSO) were used as the sensitivity analyses. Our results suggested that higher levels of monocyte‐specific chemokine‐3 (IVW estimate odds ratio ORIVW per SD genetic cytokines change: 1.24; 95% confidence interval CI: 1.03‐1.49; P = .02), vascular endothelial growth factor (1.14, 1.03‐1.27; P = .02), interleukin‐10 (1.33, 1.01‐1.75; P = .04) and interleukin‐7 (1.24, 1.03‐1.48; P = .02) were associated with increased risk of MM, while lower levels of tumor necrosis factor‐β (0.84, 0.74‐0.92; P < .001) was strongly associated with an increased risk of MM. And conversely, genetically predicted MM was related to increased levels of interleukin‐17 (IVW estimate β: 0.051, 95% CI: 0.018‐0.085; P = 2.7 × 10−3). Besides, we observed no such significant associations for other inflammatory factors in our study. Overall, our study provides genetic evidence on the relationships of CRP and systemic inflammatory regulators with MM. Targeted interventions of specific inflammatory factors may have implications to alleviate MM cancer risk.
What's new?
Observational studies have demonstrated strong associations between C‐reactive protein (CRP), inflammatory regulators and multiple myeloma, but the direction of causality remains unclear. Here, the authors designed a bidirectional Mendelian randomization analysis using summary‐level data of human cytokines and CRP from two genome‐wide association studies (GWASs) and a GWAS summary‐level data of multiple myeloma. They identified MCP3, VEGF, IL‐10, IL‐7 and TNF‐β as five upstream determinants and IL‐17 as one downstream factor for multiple myeloma. The findings suggest a causal association between inflammation and multiple myeloma (MM) and provide novel clues on the aetiology, prevention and prognosis of multiple myeloma.
Background and Aims
Antihypertensive drugs were recently reported to have an oncogenic role in common cancer, however, whether these drugs would affect the risk of hepatocellular carcinoma (HCC) ...remains unclear.
Methods
A drug‐target Mendelian randomization method was adopted to examine the long‐term effect of 12 antihypertensive drugs classes on the risk of HCC in Europeans and East Asians. To proxy antihypertensive drugs, we leveraged genetic variants located near or within drug target genes that were associated with systolic blood pressure (SBP). Genetically proxied drugs associated with reduced risk of coronary artery disease were included in primary analysis. Genetic summary statistics of SBP and HCC were derived from publicly available large‐scale genome‐wide association studies in Europeans and East Asians respectively. Expression quantitative trait loci (eQTLs) of drugs target genes were used to proxy drugs in a sensitivity analysis.
Results
Genetically proxied thiazides and related diuretics were associated with decreased risk of HCC in both Europeans (OR 95% CI: 0.79 0.73, 0.86 per 1 mmHg reduction in SBP; p < 0.001) and East Asians (0.60 0.45, 0.82; p = 0.001). Genetically proxied beta‐adrenoceptor blockers (BBs) were strongly associated with increased risk of HCC in Europeans (1.46 1.12, 1.91; p = 0.004). These findings were replicated in deCODE genetics study and remained consistent when using eQTLs to proxy antihypertensive drugs.
Conclusions
Our findings suggested that thiazides diuretics may lower the risk of HCC in both Europeans and East Asians, while BBs may increase the risk of HCC specifically in Europeans. Further studies are warranted to explore the potential of repurposing or retargeting antihypertensive drugs for HCC prevention.
Electrochemical machining (ECM) is a noncontacting method for machining complex contours that is independent of the hardness and strength of metals. Since the materials are removed in the form of ...ions via electrochemical dissolution, good surface integrity is a primary advantage of ECM. However, the selective dissolution of the metal phase and the differences in current density have significant effects on the local surface film composition and surface morphology of the machined sample. This paper focused on the morphology and the surface film composition of 1Cr11Ni2W2MoV heat-resistant steel after ECM processing. Herein, experiments were conducted with specialized fixtures. Moreover, the anodic polarization curve and current efficiency curve of 1Cr11Ni2W2MoV steel were obtained. The analysis of the experimental process and the examination of the specimens indicated that the material heterostructure and the current density seriously influenced the stability of the electrochemical dissolution process, and that carbide enrichment led to a poor-quality surface with a dense water ripple texture. Based on the experimental results, a three-layer metal dissolution model in NaNO3 solution was established. A machining current density of 30-40 A cm−2 for ECM of 1Cr11Ni2W2MoV steel was found to obtain good surface quality.
Evidence suggested strong associations between women's reproductive factors and major depressive disorder (MDD), but their causalities are unclear.
Using female-specific SNPs as genetic instruments ...obtained from large-scale genome-wide association studies for women's reproductive traits, we designed two-sample univariable and multivariable Mendelian randomization (MR) analysis to evaluate the causal effects of women's reproductive traits on MDD. For both univariable MR (UVMR) and multivariable MR (MVMR), the inverse variance weighting estimates were reported as main results. MR-Egger, weighted median, and generalized summary-data-based MR (GSMR) methods for UVMR, and MVMR-Egger and MVMR-robust methods for MVMR were used as sensitivity analyses. Negative control analyses, MVMR of age at first birth (AFB) and age at first sexual intercourse (AFS) on MDD, and sex-combined genetic variants for AFB and AFS were performed to enhance the robustness of our study.
There was substantial evidence for associations of genetically predicted later age at menarche (AAM) (odds ratio (OR) = 0.97, 95 % confidence interval (CI) = 0.94–0.99, P = 0.007), AFB (OR = 0.91, 95 % CI = 0.86–0.97, P = 0.002) and AFS (OR = 0.70, 95 % CI = 0.60–0.80, P < 0.001) with lower MDD risk in UVMR. After adjustment of BMI and educational attainment using MVMR, we found consistently significant causal effects of AAM (OR = 0.95, 95 % CI = 0.92–0.99, P = 0.006), AFB (OR = 0.88, 95 % CI = 0.84–0.91, P < 0.001) and AFS (OR = 0.71, 95 % CI = 0.64–0.79, P < 0.001) on MDD.
Our results provide compelling evidence that early AAM, AFB, and AFS are risk factors for MDD. Promoting the cognition of reproductive health care for women may reduce the risk of MDD.
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•Causal relationships between women’s reproductive factors and major depressive disorder (MDD) were first evaluated.•Consistent evidence supports adverse effects of earlier at menarche, first birth and first sexual intercourse on MDD.•Our results promote the cognition of reproductive health care for women may reduce the risk of MDD.
As a new analogy paradigm of human learning process, reinforcement learning (RL) has become an emerging topic in computational intelligence (CI). The synergy between the RL and CI is an emerging way ...to develop efficient solution algorithms for solving complex combinatorial optimization (CO) problems like machine scheduling problem. In this paper, we proposed an efficient optimization algorithm based on Deep RL for solving permutation flow-shop scheduling problem (PFSP) to minimize the maximum completion time. Firstly, a new deep neural network (PFSPNet) is designed for the PFSP to achieve the end-to-end output without limitation of problem sizes. Secondly, an actor-critic method of RL is used to train the PFSPNet without depending on the collection of high-quality labelled data. Thirdly, an improvement strategy is designed to refine the solution provided by the PFSPNet. Simulation results and statistical comparison show that the proposed optimization algorithm based on deep RL can obtain better results than the existing heuristics in similar computational time for solving the PFSP.
In this article, we demonstrated the fabrication of 3D p-type CuO nanowires (NWs)/intrinsic hydrogenated amorphous silicon(i-a-Si:H) Ridial Hetero-juntion Solar Cells(RHSC) for the first time. we ...also obtained different composition of oxide NWs and different lengths of NWs by controlling the growing time and temperature upon low-cost stainless steel substrates. A highly p-doped a-Si:H thin film was introduced as a passivation layer to establish more depletion and decrease the leakage at hetero-interface. Photovoltaic(PV) property with a high open-circuit voltage of 740mV has been reached for the cell, which is higher than that of solar cells fabricated with CuO-based planner structure.
Abstract The configuration of the detection head has a significant impact on detection performance. However, when the input resolution or detection scene changes, there is not a clear method for ...quantitatively and efficiently configuring the detection head. We find that there is a rule of matching degrees between the object scale and the detection head across different input resolutions or detection scenes by careful analysis. Based on this matching rule, we propose simple yet very effective methods for detection head configuration. The methods consist of two main parts. The first is the matching strategy of detection head and object scale, which can handily and quantitatively guide the rational configuration of detection heads to effectively detect objects at vastly different scales. The second is the skip-scale detection head configuration guideline, which instructs to replace multiple detection heads with only two detection heads to decrease model parameters as well as achieve high detection accuracy and speed. Extensive experimental results on three benchmarks, BDD100K, nuImages and our proposed ETFOD-v2, validate the effectiveness and convenience of our proposed methods, showing potential application prospect in future intelligent traffic systems. The code and ETFOD-v2 dataset are available in https://github.com/YiShi701/MR-Net .
Low-light image enhancement aims to improve the perceptual quality of images captured in conditions of insufficient illumination. However, such images are often characterized by low visibility and ...noise, making the task challenging. Recently, significant progress has been made using deep learning-based approaches. Nonetheless, existing methods encounter difficulties in balancing global and local illumination enhancement and may fail to suppress noise in complex lighting conditions. To address these issues, we first propose a multi-scale illumination adjustment network to balance both global illumination and local contrast. Furthermore, to effectively suppress noise potentially amplified by the illumination adjustment, we introduce a wavelet-based attention network that efficiently perceives and removes noise in the frequency domain. We additionally incorporate a discrete wavelet transform loss to supervise the training process. Particularly, the proposed wavelet-based attention network has been shown to enhance the performance of existing low-light image enhancement methods. This observation indicates that the proposed wavelet-based attention network can be flexibly adapted to current approaches to yield superior enhancement results. Furthermore, extensive experiments conducted on benchmark datasets and downstream object detection task demonstrate that our proposed method achieves state-of-the-art performance and generalization ability.
